Mandrekar P, Catalano D, Szabo G
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
Alcohol Clin Exp Res. 1997 Sep;21(6):988-94.
Acute ethanol exposure has the capacity to modulate immune functions, particularly, to down regulate monocyte production of inflammatory cytokines. However, the intracellular mechanisms for these effects of ethanol are yet to be understood. Considering that nuclear regulatory factor-kappa beta (NF-kappa B)/Rel is a common regulatory element of the promoter region of the inflammatory cytokine genes, herein, we tested the hypothesis that acute ethanol affects NF-kappa B activation in human monocytes. Adherence-isolated monocytes showed constitutive DNA binding activity of NF-kappa B. A clinically relevant dose (25 mM) of acute ethanol treatment in vitro increased NF-kappa B binding activity in monocytes with a preferential induction of the inhibitory, p50/p50, NF-kappa B/Rel homodimer, and resulted in no induction of the p65/p50 heterodimer. In contrast, lipopolysaccharide stimulation primarily induced the p65/p50 heterodimer that has been shown to result in gene activation. Thus, such unique activation of the inhibitory p50/p50 homodimer by acute ethanol treatment may result in inhibition rather than activation of NF-kappa B-regulated inflammatory cytokine genes. Consequently, these results suggest that physiologically relevant concentrations of ethanol may affect production of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 by disrupting NF-kappa B signaling in monocytes.
急性乙醇暴露能够调节免疫功能，尤其是下调单核细胞炎性细胞因子的产生。然而，乙醇产生这些效应的细胞内机制尚不清楚。鉴于核调节因子-κB（NF-κB）/Rel是炎性细胞因子基因启动子区域的常见调节元件，在此，我们检验了急性乙醇影响人单核细胞中NF-κB激活的假说。贴壁分离的单核细胞显示出NF-κB的组成性DNA结合活性。体外给予临床相关剂量（25 mM）的急性乙醇处理可增加单核细胞中NF-κB的结合活性，优先诱导抑制性的p50/p50 NF-κB/Rel同二聚体，且不会诱导p65/p50异二聚体。相反，脂多糖刺激主要诱导已被证明可导致基因激活的p65/p50异二聚体。因此，急性乙醇处理对抑制性p50/p50同二聚体的这种独特激活可能导致NF-κB调节的炎性细胞因子基因受到抑制而非激活。因此，这些结果表明，生理相关浓度的乙醇可能通过破坏单核细胞中的NF-κB信号传导来影响炎性细胞因子如肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6的产生。
